HVJ-liposome mediated gene transfer into hepatocytes in vivo.

HVJ-liposome mediated gene transfer into hepatocytes in vivo.
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HVJ-脂质体介导的体内基因转移至肝细胞。

DOI:
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发表时间:
1998
影响因子:
25.7
通讯作者:
Y. Kaneda
Y. Kaneda
中科院分区:
医学1区
文献类型:
--
作者:
T. Hirano;J. Fujimoto;T. Ueki;H. Yamamoto;M. Takeuchi;E. Okamoto;H. Takahashi;R. Morisita;Y. Sawa;Y. Kaneda

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背景/目标 适当靶细胞的有效转导对于基因治疗至关重要。我们评估了日本血凝病毒(HVJ)脂质体介导的基因转移对于肝病基因治疗的适用性。 方法 通过 HVJ 脂质体将大肠杆菌 β-半乳糖苷酶 (β-gal) 基因导入大鼠肝脏,以检查转染前是否进行部分肝切除的基因转移功效和表达的持续性。 结果 门静脉注射后约30%的肝细胞被转导。基因表达是短暂的,4 周后只有 2% 的肝细胞表达 β-gal。然而,注射前 24 小时进行部分肝切除术导致注射后 4 周内 β-gal 水平持续较高。在转染大鼠的肝脏中检测到 247-bp β-gal 聚合酶链式反应片段转录本,但在对照大鼠的肝脏中未检测到。基因转移后的大鼠肝脏组织学正常,并且未发现大鼠血清谷氨酸-丙酮酸转氨酶升高。 结论 我们的结果表明,HVJ 脂质体介导的基因转移在肝脏中产生了高基因转导和持久的基因表达。
BACKGROUND/AIMS The efficient transduction of appropriate target cells will be critical for gene therapy. We evaluated the suitability of hemagglutinating virus of Japan (HVJ)-liposome-mediated gene transfer for gene therapy of liver diseases. METHODS The Escherichia coli beta-galactosidase (beta-gal) gene was introduced into rat liver by HVJ-liposome to examine gene transfer efficacy and persistence of expression with or without partial hepatectomy prior to transfection. RESULTS About 30% of hepatocytes were transduced after portal vein injection. Gene expression was transient, with only 2% of hepatocytes expressing beta-gal after 4 weeks. However, partial hepatectomy performed 24 h prior to injection resulted in persistently high levels of beta-gal for 4 weeks after injection. A 247-bp beta-gal polymerase chain reaction fragment transcript was detected in livers of transfected rats, but not in livers of control rats. The rat livers following gene transfer were histologically normal, and serum glutamic-pyruvic transaminase was not found to be elevated in rats. CONCLUSIONS Our results demonstrate that HVJ-liposome-mediated gene transfer produced high gene transduction and persistent gene expression in the liver.
DOI: 10.1089/hum.1993.4.4-403
发表时间: 1993-08-01
期刊: HUMAN GENE THERAPY
影响因子: 4.2
作者:
LI, QT;KAY, MA;WOO, SLC
通讯作者: WOO, SLC
DOI: --
发表时间: 1994
期刊: Blood
影响因子: 20.3
作者:
S. Goodman;X. Xiao;R. Donahue;A. Moulton;J. Miller;C. Walsh;N. Young;R. Samulski;A. Nienhuis
通讯作者: S. Goodman;X. Xiao;R. Donahue;A. Moulton;J. Miller;C. Walsh;N. Young;R. Samulski;A. Nienhuis
DOI: 10.1073/pnas.92.5.1470
发表时间: 1995-02-28
影响因子: 11.1
作者:
TAKAHASHI, H;FUJIMOTO, J;ISSELBACHER, KJ
通讯作者: ISSELBACHER, KJ